title: Subchondral cyst development and MMP-1 expression during progression of osteoarthritis: an immunohistochemical study.
abstract: BACKGROUND
  Subchondral bone cyst (SBC) formation is often identified in patients with osteoarthritis. Furthermore, several studies have shown that expression of matrix metalloproteinases (MMPs) is elevated in patients with OA.
  
  
  OBJECTIVE
  The aim of our study is to correlate the presence of SBCs and MMP-1 expression with the osteochondral alterations during OA progression.
  
  
  METHODS
  We studied the cartilage and subchondral bone of 15 patients who had undergone total knee or hip replacement due to primary OA. As controls, we used the femoral heads of three patients without macroscopic OA changes. We evaluated three specimens per patient.
  
  
  RESULTS
  Specimens were divided in four groups based on the Mankin histological severity score. Using immunohistochemistry, we noted SBCs at the site of greatest disease severity. Specifically, these were present more frequently in group III (Mankin score: 6-7) and IV (Mankin: ≥ 8), compared with group I (Mankin: 1-3) and II (Mankin: 4-5). Mild OA stages (Mankin: 1-6) were characterized by degeneration and thinning of the cartilage, followed by increased osteoblast and osteoclast activity of the subjacent bone and the subsequent appearance of SBCs. Simultaneously, we observed expression of MMP-1 in groups I and II in the cartilage and III and IV in both the cartilage and the subchondral bone. Moreover, osteoblast-like cells in the lining of the SBCs showed an increased expression of MMP-1 in stages III and IV.
  
  
  CONCLUSIONS
  Our study provides immunohistological evidence that SBCs accumulate in advanced OA and contain activated cells, which express MMP-1, suggesting that they may thus participate in the osteochondral changes of OA.
  
  
  METHODS
  Level III; prospective comparative study.
authors.affiliation: Department of Trauma and Orthopaedics, Thriasio General Hospital of Attica - NHS, G. Gennimata avenue, Magoula, 19600 Athens, Greece. angkaspiris@hotmail.com
authors.forename: A
authors.initials: A
authors.lastname: Kaspiris
authors.forename: L
authors.initials: L
authors.lastname: Khaldi
authors.forename: T B
authors.initials: TB
authors.lastname: Grivas
authors.forename: E
authors.initials: E
authors.lastname: Vasiliadis
authors.forename: I
authors.initials: I
authors.lastname: Kouvaras
authors.forename: S
authors.initials: S
authors.lastname: Dagkas
authors.forename: E
authors.initials: E
authors.lastname: Chronopoulos
authors.forename: E
authors.initials: E
authors.lastname: Papadimitriou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D001845:Bone Cysts / Q000201:enzymology / Q000473:pathology* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000201:enzymology / Q000473:pathology*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D015207:Osteoarthritis, Hip / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020370:Osteoarthritis, Knee / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D011379:Prognosis
chemical_list: D015415:Biomarkers; D020781:Matrix Metalloproteinase 1
keywords: Immunohistochemistry; MMP-1; Osteoarthritis; Subchondral bone cysts